title: Haplotype analysis of Lrrk2 R1441H carriers with parkinsonism.
abstract: The Roc domain of the Lrrk2 protein harbors two pathogenic mutations which cause autosomal dominant parkinsonism (R1441C and R1441G). A third putatively pathogenic variant (R1441H) has been identified in four probands of diverse ethnicity with parkinsonism. Herein we show that the R1441H substitutions lie on different haplotypes within our patients, confirming this codon as a mutational hotspot. The absence of this variant in control subjects and the presence of two other pathogenic variants at this amino acid position collectively support the contention that R1441H is a pathogenic substitution.
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA. ross.owen@mayo.edu
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.forename: Cleanthe
authors.initials: C
authors.lastname: Spanaki
authors.forename: Alida
authors.initials: A
authors.lastname: Griffith
authors.forename: Chin-Hsien
authors.initials: CH
authors.lastname: Lin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kachergus
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Haugarvoll
authors.forename: Helen
authors.initials: H
authors.lastname: Latsoudis
authors.forename: Andreas
authors.initials: A
authors.lastname: Plaitakis
authors.forename: Joaquim J
authors.initials: JJ
authors.lastname: Ferreira
authors.forename: Cristina
authors.initials: C
authors.lastname: Sampaio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bonifati
authors.forename: Ruey-Meei
authors.initials: RM
authors.lastname: Wu
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
mesh_terms: D000328:Adult; D001120:Arginine / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006639:Histidine / Q000235:genetics; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D006639:Histidine; D001120:Arginine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases